This project concerns the development of laser differential light scattering spectrophotometry as an experimental technique for the in vitro monitoring of the sickling process. During the past year, the laser differential light scattering system developed in our laboratory was improved by incorporating a krypton ion laser with the system. A unique feature of the krypton ion laser is that it offerred two output wavelengths (799.3 nm and 568.2nm) which are the isosbestic wavelengths for oxy- and deoxy- hemoglobin. By employing either of the two wavelengths, experiments were conducted which show that the differential light scattering patterns were independent of the hemoglobin oxygen saturation of the blood sample, but only a function of the red cell shape and volume. Extensive experiments were conducted with this laser differential light scattering system to characterize the reproducibility and sensitivity of the system to study red cell morphology. Studies were also carried out to investigate design of suitable optical cuvettes leading to the design of a semicircular cuvette which greatly reduce any stray light due to internal reflection. Differential light scattering patterns at the two isosbestic wavelengths of 568 and 799 nm were obtained systematically for normal red cells at a hematocrit range from 0.5 to 2.5% for different sample pH and oxygen saturation. Work is now in progress to obtain differential light scattering patterns of sickle cells for comparison with those of normal cells. A new detector system incorporating multi photodiodes are also being designed in order for the rapid acquisition of differential light scattering pattern. With the new multidetector system, we plan to carry out dynamic study with sickle cells employing rapid reaction technique.